• Catherine Steele

Understanding Clinical Trials for People with Cancer

Advice on finding suitable clinical trials, how to enrol and some important factors that you should consider before agreeing to participate.

Yesterday I received a radiologist’s report from the Christie Hospital in Manchester. I’m delighted to say that my cancer burden remains very low and is stable.

I have been participating in the HER2CLIMB clinical trial for 15 months and it has been a huge success for me. The trial is designed to determine whether the addition of the trial drug (Tucatinib) with an existing treatment combination (Capecitabine and Trastuzumab) increases Progression Free Survival (PFS) and other survival markers. The average PFS for the combination of Capecitabine with Trastuzumab is 28 weeks which is less than half the time that I have been on the trial.

Furthermore, despite being my third line of treatment for metastatic breast cancer, it has been almost twice as effective as my first two lines of treatment (which each kept me stable for 8 or 9 months).

HER2CLIMB is a double-blind trial which means that neither I or my medical team know whether I’m receiving the trial drug or a placebo, but with these results, I strongly suspect that I am part of the cohort receiving the trial drug.

It’s not been easy though. Manchester is 400 miles away from my home in Aberdeenshire and every three weeks, I have to take the trip alone to be treated, tested, poked and prodded. The side effects are unpleasant, but manageable but the scan schedule is relentless.

I realise that not everyone has such success with trials. By nature, the risks involved for patients participating in clinical trials are high, especially in earlier phases where safe dosing levels have not yet been established. Indeed, I had a friend who embarked on a phase 1 immunotherapy trial last year and sadly died weeks later from a phenomenon known as hyper-progression. My personal success is tinged with guilt and sadness for others who have not been as lucky as me.

Embarking on a clinical trial is a big decision. In this blog, I share some tips for finding suitable clinical trials, how to enrol and some important factors that you should consider before agreeing to participate.

1. What is a Clinical Trial?

Before a treatment is licensed, it is subjected to rigorous testing to ensure it is safe and effective. This testing starts in the lab on cell cultures and animal models (usually mice). Once efficacy is demonstrated, the organisation must apply for a licence from an independent government body to allow the drug to be administered to humans as part of a clinical trial. It is a long and arduous process with a high failure rate. Only 1 in every 1000 drugs progress from pre-clinical testing to clinical trial.

2. When to seek Clinical Trial

The short answer is ‘anytime’. I’ve heard oncologists recommend that you should only consider clinical trials once all the standard treatment options have been exhausted. In my view, this is nonsense and can have a serious detrimental effect on prognosis. I am constantly on the lookout for trials that I might qualify for as they often offer the possibility of an enhanced protocol compared to the standard treatment options. This is especially true of later phase trials where the trial drug is given as an adjunct to the standard protocol rather than an alternative. The HER2CLIMB trial that I’m participating in is a perfect example.

Before starting any new treatment, I always check whether there are any trials that I may qualify for. This is important because often the exclusion criteria does not allow participants who have already had certain treatments. If you are lucky enough to have a choice of treatment options, this research is vital so that you don’t inadvertently exclude yourself from a possibly life-extending trial.

3. Finding a Suitable Clinical Trial

There are various databases where you can search for clinical trials based on cancer type, location and drug/trial name. A good example is that provided by Cancer Research UK (https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial), though personally I have found the search facility and information provided on the American based site https://clinicaltrials.gov to be better.

It is a good idea to narrow your search to your home country and include any biomarkers in your search criteria.

As an NHS patient, you are not restricted to trials within n your local healthcare region. You are free to apply to trials anywhere in the UK. Usually the trial sponsor will pay for travel expenses within your home country. I have known people also to participate in trials as far away as Japan, but obviously cost and upheaval becomes a bigger issue when considering trials abroad.

Private healthcare policies do not generally provide cover for clinical trials. If you do have private healthcare you can still retain your policy and your cover (assuming you choose to continue paying the premiums) but you are likely to have to transfer your care to the NHS for the duration of the trial.

4. Understanding the Phases of a Trial

Clinical trials are categorised into five phases (0-4). Earlier phases tend to carry more risk and are conducted on fewer patients. Their primary outcome is to ensure the treatment isn’t harmful, the side effects are tolerable and to determine the most effective dose. Once a trial reaches stage 3 or 4, there is more information known about the safety profile of the drug, the dosing strategy and the likely side effects. Generally speaking, you are exposing yourself to more risk for early phase trials and less risk for late phase trials.

It is also easier to enrol on late phase trials as they recruit more patients and are usually conducted across many different cancer centres to rule out any location bias such as ethnicity and lifestyle.

5. Understanding the Design of a Trial

The ‘study design’ section of the clinical trial details will include information about the Allocation, Intervention Model and Masking. It is important to understand these terms when considering whether to participate.

Allocation - Treatment allocation is either randomised or non-randomised. Early phase trials tend to be non-randomised, meaning that patients are allocated to treatment protocols by the investigator. In randomised trials, participants are randomly allocated different protocols. The process of randomisation helps to minimise bias in results.

Intervention Model - This term refers to the protocol design. For example, a single-group assignment means that all patients receive the same treatment. Parallel assignment is used when researchers want to compare two or more drugs. The study I am participating in uses a parallel assignment model because the primary aim of the study is to determine whether the addition of the trial drug results improves survival. The participants are divided into two groups - one that receives the trial drug and one that receives a placebo. Other less common intervention models are cross-over assignment and factorial assignment.

Masking - The different masking strategies refer to which parties involved in the trial know who has been assigned what treatment. In open-label trials, all parties are aware of the assignments. In single-blind masking, the patient does not know which cohort they have been assigned to, but this information is available to the medical professionals and the study sponsors. In a double-blind study, neither the patient, the medical professionals or the study sponsors know how different treatments have been assigned. Double-blind trials can be unnerving for participants but are the norm when comparing one treatment against another.

6. Applying for a Trial

Before applying for a trial, you should speak with your oncologist to get their view on whether the trial is suitable for you. He or she may raise factors that you haven’t thought of and will need to liaise with the sponsors during the enrolment process.

You may either contact the trial team directly or ask your oncology team to do this on your behalf. In my case, and with the backing of my oncologist, I took the direct approach as I felt that progress would be quicker that way. Throughout the enrolment process I kept in touch with my oncologist’s secretary and the trial team to ensure that they both had everything they needed as quickly as possible.

The enrolment process usually involves a lot of scans to confirm that you pass the eligibility criteria and to provide a baseline upon which to judge the success of the treatment.

7. Trial restrictions

The conditions of most trials state that you are not permitted to take any other medication except that which has been approved by the sponsor. This can include any complementary therapies, off-label drugs and supplements. These restrictions are necessary so that the impact of the intervention can be isolated from any other factors.

Before starting my trial, I was taking a number of supplements and was considering adding off-label drugs to my daily cocktail. I made a judgement call that the possible advantages that I would gain from the trial outweighed the impact that the supplements and off-label drugs would have.

Ultimately, clinical trials are risky. There is no guarantee of success and the long-term effects of the drugs are not known. On the other hand, I’ve heard many stories of people achieving remarkable results and even long-term remission through participation in a trial. They are also vital to the ongoing development of life-saving and life-extending drugs, so by participating in a trial, you are helping future cancer patients get access to new and improved treatments.

The decision to participate in a clinical trial must be made on a case by case basis, taking into consideration, not just your physical situation, but also wider aspects involved in the quality of your life.

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